By David Brown
Washington Post Staff Writer
Tuesday, July 20, 2010; A01
A woman's risk of infection with the AIDS virus can be significantly cut by the use of a vaginal gel, a study has found. The research marks the first success in a 15-year search for a way women can independently protect themselves from contracting HIV infection through sex.
Short of a vaccine, an effective vaginal microbicide has been the most elusive goal in the epidemic.
The research, which was conducted in South Africa and will be presented Tuesday at the 18th International AIDS Conference in Vienna, tested a gel containing the antiretroviral drug tenofovir. While far from perfect, it was unambiguously helpful, reducing the risk of HIV infection by 39 percent in a group of women who used it for about three-quarters of their sexual encounters. Those who used it more consistently experienced 54 percent fewer infections.
If development follows the expected course, more-potent formulations, combined with campaigns to make the product appealing (or even sexy), could result in vastly better protection.
Of the 33 million people worldwide infected with the AIDS virus, 16 million are women. In Africa, 60 percent of people with HIV infection are women, nearly all of whom acquired the virus through sex. For many, the proven methods of preventing infection, such as abstinence, being faithful and using condoms, are either not an option or out of their control. A vaginal microbicide that could be used with or without a man's knowledge is considered essential, missing until now.
News of the results of the Caprisa-004 study, which leaked out a day before they were to be presented, sent a wave of optimism through the AIDS research community.
"We have never had any kind of tool that has effectively allowed women to protect themselves," said Bruce Walker, an AIDS researcher at Harvard Medical School. "This is really a game-changer."
"It's groundbreaking," said Catherine Hankins, chief scientific officer of the United Nations' AIDS agency, UNAIDS. "This in combination with [male] circumcision in places where the epidemic is generalized could really turn the tide."
"Everyone is just delighted. There were a lot of skeptics that the concept would work at all," said Zeda Rosenberg, head of the International Partnership for Microbicides in Silver Spring.
Researchers would need to show that the microbicide is effective in at least one other group of women before it could be licensed for commercial use, several people said Monday. That effort now climbs to the top of the international research agenda, although at a minimum the work will take several years.
A larger study testing tenofovir gel and antiretroviral drugs in pill form as a way to protect women against sexual transmission of HIV is underway in four African countries but will not be finished until 2013. Several other experiments, including ones in which the drug is in a long-acting vaginal ring, are in earlier stages. A microbicide might also be useful in protecting men who acquire the virus through anal sex.
"I think the big challenge is to get confirmatory studies done quickly," Hankins said.
Over the past 15 years, six other microbicides were tested in 11 clinical trials, with none showing protection.
The net impact seen in the study reflects the combined effect of many variables, only one of them the action of tenofovir, which penetrates into the vaginal tissue, protecting the cells that HIV targets for infection. Other variables include the prevalence of HIV infection in the male population; the number of sexual partners a woman had; the amount of AIDS virus ("viral load") in an infected man's semen; concurrent use of condoms; and, most important, the consistency with which a woman used the gel.
For that reason, the researchers said, it's impossible to say how much protection this microbicide might afford any woman.
"We can only approximate it," said Salim Abdool Karim of the University of KwaZulu-Natal in Durban, South Africa, who helped lead the study. "What you see is a mixture of the efficacy of the product mixed with the ability to use the product. It is fundamentally dependent on human behavior."
In the study, a group of HIV-negative women (both city dwellers and rural villagers) were randomly assigned to use a gel that was either 1 percent tenofovir gel or a placebo gel.
The material came packed in syringe-like applicators. A woman was instructed to inject the gel into her vagina no more than 12 hours before intercourse and again within 12 hours afterward (but with no more than two applications in a 24-hour period). Each woman got a monthly AIDS test, and the researchers collected used and unused applicators to verify the women's reports of whether they were using them.
At the end of 2 1/2 years, there were 98 infections in the 889 women. The HIV incidence, measured as the number of new infections for every 100 "women years" in the study, was 5.6 in the volunteers using the tenofovir gel and 9.1 in those with the placebo gel.
That amounted to a prevention effectiveness of 39 percent. Among women who said they used the gel for at least 80 percent of episodes of intercourse, the effectiveness was 54 percent.
Why the drug-containing gel did not work even better perplexed some scientists and will probably be a subject of more study.
"My most likely explanation is that you have to go up on the dose," said Anthony S. Fauci, who heads the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. "You may have maxed out on 1 percent," he said, meaning a more concentrated gel might produce greater protection.
Other scientists speculated that some women who became infected despite using the tenofovir gel might have been exposed to men with very high HIV load (which occurs soon after infection). Others may have had vaginal sores or inflammation that raised their vulnerability.
The Caprisa study also looked at whether tenofovir gel decreased a woman's risk of getting genital herpes, a virus that increases her chance of acquiring HIV if she has intercourse with an HIV-infected man.
Tenofovir provides some protection. Half as many women using gel with the drug in it became infected as did those using the placebo gel.